The amphipathic α-helix concept Application to the de novo design of ideally amphipathic Leu, Lys peptides with hemolytic activity higher than that of melittin

AbstractAn original serie of 12- to 22-residue-long peptides was developed, they are only constituted by apolar Leu and charged Lys residues periodically located in the sequence in order to generate ideal highly amphipathic α-helices. By circular dichroism, the peptides are proven to be mainly α-helical in organic and aqueous solvents and in the presence of lipids. The peptides are highly hemolytic, their activity varies according to the peptide length. The 15-, 20-, and 22-residue-long-peptides have LD50 ∼5 × 10−8 M for 107 erythrocytes, i.e. they are 5–10 times more active than melittin, and are indeed several orders of magnitude more active than magainin or mastoparan